A Hybrid Nanovector of Suicide Gene Engineered Lentivirus Coated with Bioreducible Polyaminoglycosides for Enhancing Therapeutic Efficacy against Glioma. (18th January 2019)

• Record Type: Journal Article
• Authors: Fan, Wenhua; Shao, Meiyu; Zhang, Junwen; Jin, Guishan; Liu, Fusheng; Xu, Fu‐Jian
• Is Part Of: Advanced functional materials. Volume 29:Number 11(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-01-18
• Subjects: aminoglycoside -- glioma -- hybrid nanovector -- lentivirus -- suicide gene; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201807104
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: An emerging hybrid nanovector integrating the merits of both viral and nonviral vectors has attracted much attention as the next generation of promising gene vectors to overcome the primary challenge of cancer gene therapy. Due to its inherent advantages, lentivirus (Lv) has been increasingly applied and investigated in medical fields. Herein, a new hybrid nanovector (SS‐HPT/Lv) composed of the Lv core and reduction‐responsive hyperbranched polyaminoglycoside (SS‐HPT) shell is designed via electrostatic interaction. In comparison with polybrene (commercial enhanced transfection reagent), SS‐HPT endows the hybrid nanovector with better biosafety. Furthermore, both the appropriate nanoparticle sizes and positive surface potentials contribute to the endocytosis and rescue of SS‐HPT/Lv from endocytic vesicles. Regarding therapeutic application, lentiviral vector acquires permanent transgene expression with the capability of integrating to the host chromosome, and SS‐HPT/Lv exhibits an improved transduction efficacy. The cytosine deaminase/5‐fluorocytosine suicide gene therapy system mediated by SS‐HPT/Lv performs an enhanced antitumor efficiency and extends the survival time of glioma‐bearing rats. Such a hybrid nanovector strategy would open a new avenue to the development of gene vectors for treating malignant cancers. Abstract : An effective hybrid nanovector based on the suicide gene engineered lentivirus and bioreducible polyaminoglycosides is designed to enhance therapeutic efficacy against glioma. Such a hybrid nanovector integrating the merits of both viral and nonviral vectors exhibits good biocompatibility and enhanced transduction performance as well as effective antitumor effect in vitro and in vivo.